The small hepatitis B virus surface antigen (HBsAg)
is the major constituent of the envelope of hepatitis B virus and is composed
of 226 amino acids. The proposed topology of HBsAg shows that it consists of
four membrane-spanning helices and two hydrophilic exposed segments. The second
hydrophilic domains residing in residues 124-137 and 139-147 has been
identified to contain the main conformational epitopes and is defined the “a”
determinant of the S antigen. Furthermore, vaccinated children who cannot gain
protection against chronic infection were found to harbor several HBV variants
possessing the altered antigenic epitopes. Among these HBV variants, the most
frequently found variant is Arg145 instead of the native Gly145
of S antigen. In the present study, we carried out the structural studies of
the small circular epitope linked by a disulfide bridge, HBsAg139-147
and its G145R mutant in the aqueous solution as well as in 30% TFE using NMR
and CD experiments. Multiple conformers were identified for both HBsAg139-147
and G145R mutant due to the cis/trans isomerization of Pro142,
and the trans/cis ratio was increased for both peptides when the sample
temperature was increased. Based on the 3D solution structures generated using
X-PLOR program, the conformational differences between HBsAg139-147
and G145R mutant are discussed.